There is strong evidence from our earlier studies that the infusion of ischemic myocardium with glucose-insulin-potassium mixture decreases the infarct size and results in minimal injury to the myocardial cell. This finding has stimulated a great interest in exploring other therapeutic agents and their effects on the ultrastructure of ischemic myocytes. We intend to investigate in depth the structural, functional and metabolic characteristics of the ischemic cells and to determine the critical period of acute ischemia during which the cell injury can be modified with therapeutic interventions. The changes in serum enzyme levels are an indication of injury to the myocardial cells during ischemia and constitutes one of the clinical means of detecting myocardial infarction. It is not yet established how the enzyme release is related to the ultrastructural defects in plasma and other cell membranes. The intracellular membranes play a critical role in the pathogenesis of cell injury, therefore these membranes will be examined by freeze-fracture technique. The particles (70 angstrom units) which are embedded within the membranes and exposed by freeze-fracture process are reportedly associated, for example, with calcium transport enzyme in the sarcoplasmic reticulum and will be of significant value in determining the structural competence of the ischemic cells. The identical particles in other membranes may also have specific functions in the cell and their altered location, shape and number may be responsible for the pathogenecity of the membranes. Ultimately, with the use of sophisticated techniques a structural-functional relationship may be more meaningful in understanding the acute ischemic changes and their reversibility characteristics.